ETV4 is a mechanical transducer linking cell crowding dynamics to lineage specification DOI Creative Commons
Seungbok Yang, Mahdi Golkaram,

Seyoun Oh

и другие.

Nature Cell Biology, Год журнала: 2024, Номер 26(6), С. 903 - 916

Опубликована: Май 3, 2024

Dynamic changes in mechanical microenvironments, such as cell crowding, regulate lineage fates well proliferation. Although regulatory mechanisms for contact inhibition of proliferation have been extensively studied, it remains unclear how crowding induces specification. Here we found that a well-known oncogene, ETS variant transcription factor 4 (ETV4), serves molecular transducer links microenvironments and gene expression. In growing epithelium human embryonic stem cells, dynamics is translated into ETV4 expression, serving pre-pattern future fates. A switch-like inactivation by derepresses the potential neuroectoderm differentiation epithelia. Mechanistically, inactivates integrin-actomyosin pathway blocks endocytosis fibroblast growth receptors (FGFRs). The disrupted FGFR marked decrease protein stability through ERK inactivation. Mathematical modelling demonstrates density precisely determines spatiotemporal expression pattern and, consequently, timing geometry development. Our findings suggest drives specification using key transducer.

Язык: Английский

Mechanisms of human embryo development: from cell fate to tissue shape and back DOI Creative Commons
Marta N. Shahbazi

Development, Год журнала: 2020, Номер 147(14)

Опубликована: Июль 15, 2020

Gene regulatory networks and tissue morphogenetic events drive the emergence of shape function: pillars embryo development. Although model systems offer a window into molecular biology cell fate shape, mechanistic studies our own development have so far been technically ethically challenging. However, recent technical developments provide tools to describe, manipulate mimic human embryos in dish, thus opening new avenue exploring Here, I discuss evidence that supports role for crosstalk between during early embryogenesis. This is critical developmental period, when body plan laid out many pregnancies fail. Dissecting basic mechanisms coordinate will generate an integrated understanding embryogenesis strategies therapeutic intervention pregnancy loss.

Язык: Английский

Процитировано

165
Depletion of aneuploid cells in human embryos and gastruloids DOI Open Access
Min Yang, Tiago Rito, Jakob J. Metzger

и другие.

Nature Cell Biology, Год журнала: 2021, Номер 23(4), С. 314 - 321

Опубликована: Апрель 1, 2021

Язык: Английский

Процитировано

123
New developments in the biology of fibroblast growth factors DOI
David M. Ornitz,

Nobuyuki Itoh

WIREs Mechanisms of Disease, Год журнала: 2022, Номер 14(4)

Опубликована: Фев. 9, 2022

Abstract The fibroblast growth factor (FGF) family is composed of 18 secreted signaling proteins consisting canonical FGFs and endocrine that activate four receptor tyrosine kinases (FGFRs 1–4) intracellular (intracellular or iFGFs) primarily function to regulate the activity voltage‐gated sodium channels other molecules. FGFs, iFGFs have been reviewed extensively by us others. In this review, we briefly summarize past reviews then focus on new developments in FGF field since our last review 2015. Some highlights 6 years include use optogenetic tools, viral vectors, inducible transgenes experimentally modulate signaling, clinical small molecule FGFR inhibitors, an expanded understanding functions for stem cell pluripotency differentiation, roles tissue homeostasis regeneration, a continuing elaboration mechanisms development, expanding appreciation neuropsychiatric diseases. This article categorized under: Cardiovascular Diseases > Molecular Cellular Physiology Neurological Congenital Stem Cells Development Cancer

Язык: Английский

Процитировано

99
Amniogenesis occurs in two independent waves in primates DOI Creative Commons
Maria Rostovskaya, Simon Andrews, Wolf Reik

и другие.

Cell stem cell, Год журнала: 2022, Номер 29(5), С. 744 - 759.e6

Опубликована: Апрель 18, 2022

In primates, the amnion emerges through cavitation of epiblast during implantation, whereas in other species it does so later at gastrulation by folding ectoderm. How mechanisms amniogenesis diversified evolution remains unknown. Unexpectedly, single-cell analysis primate embryos uncovered two transcriptionally and temporally distinct waves. To study this, we employed naive-to-primed transition human pluripotent stem cells (hPSCs) to model peri-implantation development. Partially primed hPSCs transiently gained ability differentiate into cavitating epithelium that morphologically matched early amnion, fully produced resembling late instead, thus recapitulating independent differentiation The wave follows a trophectoderm-like pathway encompasses cavitation, resembles an ectoderm-like route gastrulation. discovery waves explains how could emerge via duplication pre-existing trophectoderm program.

Язык: Английский

Процитировано

77
Stem-cell-based embryo models for fundamental research and translation DOI
Jianping Fu, Aryeh Warmflash, Matthias P. Lütolf

и другие.

Nature Materials, Год журнала: 2020, Номер 20(2), С. 132 - 144

Опубликована: Ноя. 16, 2020

Язык: Английский

Процитировано

135
High-resolution transcriptional and morphogenetic profiling of cells from micropatterned human ESC gastruloid cultures DOI Creative Commons
Kyaw Thu Minn, Yuheng C. Fu, Shenghua He

и другие.

eLife, Год журнала: 2020, Номер 9

Опубликована: Ноя. 18, 2020

During mammalian gastrulation, germ layers arise and are shaped into the body plan while extraembryonic sustain embryo. Human embryonic stem cells, cultured with BMP4 on extracellular matrix micro-discs, reproducibly differentiate gastruloids, expressing markers of cells in radial arrangement. Using single-cell RNA sequencing cross-species comparisons mouse, cynomolgus monkey gastrulae, post-implantation human embryos, we reveal that gastruloids contain transcriptionally similar to epiblast, ectoderm, mesoderm, endoderm, primordial trophectoderm, amnion. Upon gastruloid dissociation, single reseeded onto micro-discs were motile aggregated same but segregated from distinct cell types. Ectodermal endodermal mixed mesodermal cells. Our work demonstrates system models primate-specific features embryogenesis, exhibit evolutionarily conserved sorting behaviors. This generates a resource for transcriptomes differentiated stereotyped

Язык: Английский

Процитировано

96
Primate gastrulation and early organogenesis at single-cell resolution DOI Creative Commons
Jinglei Zhai, Jing Guo, Haifeng Wan

и другие.

Nature, Год журнала: 2022, Номер 612(7941), С. 732 - 738

Опубликована: Дек. 14, 2022

Our understanding of human early development is severely hampered by limited access to embryonic tissues. Due their close evolutionary relationship with humans, nonhuman primates are often used as surrogates understand but currently suffer from a lack in vivo datasets, especially gastrulation organogenesis during which the major cell types dynamically specified. To fill this gap, we collected six Carnegie stage 8-11 cynomolgus monkey (Macaca fascicularis) embryos and performed in-depth transcriptomic analyses 56,636 single cells. show features perigastrulation types, help shed light on morphogenetic events including primitive streak development, somitogenesis, gut tube formation, neural patterning crest differentiation primates. In addition, comparative mouse embryoids uncovered conserved divergent across species-for example, species-specific dependency Hippo signalling presomitic mesoderm differentiation-and provide an initial assessment relevant stem models organogenesis. This comprehensive single-cell transcriptome atlas not only fills knowledge gap primate research field also serves invaluable resource for embryogenesis developmental disorders.

Язык: Английский

Процитировано

63
Human gastrulation: The embryo and its models DOI
Sabitri Ghimire, Veronika Mantziou, Naomi Moris

и другие.

Developmental Biology, Год журнала: 2021, Номер 474, С. 100 - 108

Опубликована: Янв. 20, 2021

Язык: Английский

Процитировано

58
Efficient differentiation of human primordial germ cells through geometric control reveals a key role for Nodal signaling DOI Creative Commons
Kyoung Jo, Seth Teague, Bohan Chen

и другие.

eLife, Год журнала: 2022, Номер 11

Опубликована: Апрель 8, 2022

Human primordial germ cells (hPGCs) form around the time of implantation and are precursors eggs sperm. Many aspects hPGC specification remain poorly understood because inaccessibility early postimplantation human embryo for study. Here, we show that micropatterned pluripotent stem (hPSCs) treated with BMP4 give rise to hPGC-like (hPGCLC) use these as a quantitatively reproducible simple in vitro model interrogate this important developmental event. We characterize hPSCs up 96 hr hPGCLC populations stable continue mature. By perturbing signaling during differentiation, identify previously unappreciated role Nodal find relative timing duration BMP critical parameters controlling number hPGCLCs. formulate mathematical network cross-repressive fates driven by signaling, which predicts measured fate patterns after perturbations. Finally, hPSC colony size dictates efficiency specification, led us dramatically improve differentiation.

Язык: Английский

Процитировано

47
Nodal is a short-range morphogen with activity that spreads through a relay mechanism in human gastruloids DOI Creative Commons
Lizhong Liu, Anastasiia Nemashkalo, Luisa Rezende

и другие.

Nature Communications, Год журнала: 2022, Номер 13(1)

Опубликована: Янв. 25, 2022

Abstract Morphogens are signaling molecules that convey positional information and dictate cell fates during development. Although ectopic expression in model organisms suggests morphogen gradients form through diffusion, little is known about how created interpreted mammalian embryogenesis due to the combined difficulties of measuring endogenous levels observing development utero. Here we take advantage a human gastruloid visualize Nodal protein living cells, specification germ layers. We show extremely short range so limited immediate neighborhood source cells. activity spreads relay mechanism which production induces neighboring cells transcribe Nodal. further inhibitor Lefty, while biochemically capable long-range also acts locally control timing spread therefore mesoderm differentiation patterning. Our study establishes paradigm for tissue patterning by an activator-inhibitor pair.

Язык: Английский

Процитировано

47